Biomedical subjects

A H Zwinderman

Publications and source records attributed to A H Zwinderman.

299 records · Page 17Linked to original sources

PubMedDate not supplied

No gender bias in referral for coronary angiography after myocardial perfusion scintigraphy with technetium-99m tetrofosmin.

BACKGROUND: Several studies have shown that the application of diagnostic and invasive procedures varies between men and women. The purpose of this study was to assess if referral for coronary angiography after technetium-99m tetrofosmin myocardial perfusion scintigraphy in 616 patients with undiagnosed chest pain might demonstrate gender bias. METHODS AND RESULTS: The primary end point for this study was coronary angiography within 90 days of myocardial perfusion scintigraphy. Women had more normal perfusion images than men (207 [70.9%] vs 160 [50.5%], P < .05). Of 242 patients with abnormal images (157 men, 85 women), 28 men (17.7%) and 17 women (20.0%) were referred for further invasive testing (P = not significant). Referral for coronary angiography increased relative to the number of defects. Univariate analysis showed that reversible and persistent defects were the most predictive variables for referral to coronary angiography (odds ratio [OR] 5.45, 95% confidence interval [CI] 3.10-9.58, P < .001, and OR 2.67, 95% CI 1.52-4.67, P = .001, respectively). More importantly, multivariate analysis showed that reversible perfusion defects (OR 4.77, 95% CI 2.48-9.17, P < .001) and persistent perfusion defects (OR 2.14, 95% CI 1.11-4.14, P = .02) were predictive of subsequent coronary angiography. No significant association between gender and subsequent coronary angiography was found both in univariate and multivariate logistic regression analysis (OR 0.64, 95% CI 0.37-1.12, P = .12, and OR 0.70, 95% CI 0.36-1.36, P = .28, respectively). CONCLUSIONS: Our study reveals that after correction for the presence and the severity of myocardial perfusion abnormalities, men and women were referred to coronary angiography at a similar rate. Thus, based on the results of technetium-99m tetrofosmin myocardial perfusion imaging, no substantial evidence for a gender-related bias could be found in the referral for further invasive testing.

Analysis of Variance↗

PubMedDate not supplied

Prognostic value and quality of life in patients with normal rest thallium-201/stress technetium 99m-tetrofosmin dual-isotope myocardial SPECT.

BACKGROUND: The prognostic value of normal dual-isotope single photon emission computed tomography (SPECT), with technetium 99m-tetrofosmin for the stress images, is not well known. Furthermore, thallium-201 cross talk in the Tc-99m window may reduce the defect severity of the Tc-99m images. METHODS AND RESULTS: In a consecutive series of 610 patients, 246 patients with normal rest and stress SPECT images by means of visual semiquantitative analysis were included. The patients' pre-test likelihood of coronary artery disease was determined, based on age, sex, symptoms, and the results of stress electrocardiography. Quality of life was assessed by using a mailed self-administered general quality-of-life questionnaire. We compared the mean scores (8 dimensions) of our study population with the scores of 1063 control subjects, sampled randomly out of the inhabitant register of a Dutch city. The mean follow-up period was 25+/-3 months. Compared with the control group, patients in our study scored lower (less perceived health) for all dimensions of the SF-36 (P<.05), suggesting a selection of symptomatic or otherwise diseased patients. The primary cardiac event rate was 0.4% per year. The cardiac events occurred in patients with an intermediate-to-high pre-test likelihood of disease and negative or nondiagnostic exercise electrocardiographic results. In a subset of patients with a high pre-test likelihood of coronary artery disease (more than 85%), the primary cardiac event rate was 0.7% per year. CONCLUSIONS: Patients with normal results on dual-isotope myocardial perfusion scintigraphy, performed with Tc-99m-tetrofosmin for the stress images, have an excellent prognosis. Furthermore, our results suggest that Tl-201 cross talk in the Tc-99m window may be low and functionally and clinically unimportant.

Adult↗

PubMedDate not supplied

Comparison of left ventricular function at rest and post-stress in patients with myocardial infarction: Evaluation with gated SPECT.

BACKGROUND: Quantitative electrocardiogram-gated single photon emission computed tomography (SPECT) myocardial imaging (QGS) is a means of providing functional information about the left ventricle and myocardial perfusion. However, the functional information derived 30 minutes post-stress may be different from the left ventricular (LV) function determined at rest. This study determined whether LV function post-stress would be different from LV function at rest in patients with an earlier myocardial infarction. METHODS AND RESULTS: LV perfusion and ejection fraction (LVEF), were determined by means of both the rest and post-stress acquisition in 58 patients with an earlier myocardial infarction and in 23 patients with a low likelihood of coronary artery disease by using technetium-99m tetrofosmin and the QGS program. The interobserver and intraobserver variability of LVEF was excellent, within a margin of 2%. No significant differences in LVEF were observed between post-stress and rest in the 23 patients with a low likelihood of disease (DeltaLVEF, 0.04% +/- 3.2%, P = not significant). Conversely, the patients with an earlier myocardial infarction showed a significantly lower LVEF post-stress, compared with that at rest (DeltaLVEF, -1.9% +/- 4.2%, P =.002). In 33 patients (57%), the LVEF post-stress was 2% or more lower than the LVEF at rest. Furthermore, reversible ischemia, which was present in 16 patients (28%), did not interact with the DeltaLVEF post-stress, compared with the DeltaLVEF at rest (P = not significant). Parameters such as the stress modality (adenosine stress or exercise), the number of stenosed vessels, or the perfusion defect severity score did not influence the DeltaLVEF post-stress, compared with the DeltaLVEF at rest. CONCLUSIONS: In patients with an earlier myocardial infarction, LV function post-stress may not represent the true resting LV function. Consequently, this result justifies the stratification of patients before starting the gated SPECT study. In patients with an earlier myocardial infarction, the gated acquisition should be performed during the rest study.

Adenosine↗

PubMedDate not supplied

Crossover studies with continuous variables: power analysis.

The crossover design is a sensitive means of determining the efficacy of new drugs because it eliminates between-subject variability. However, if the response in the first period carries on into the second (carryover effect) or if time factors cannot be kept constant in a lengthy crossover (time effects), its statistical power may be jeopardized. This may be equally true if a negative correlation exists between treatment responses. We recently demonstrated that the crossover design with binary variables is a powerful method even if correlation between treatment responses is negative. Power analysis of crossover trials with continuous variables has not been explicitly studied. Using the Scheffé model for the assessment of treatment effect, carryover effect, and time effect, we drew power curves of hypothesized crossover studies with different levels of correlation between drug response. We demonstrate that the sensitivity of testing is largely dependent on the levels of correlation between drug response. When positive, we have a great deal of sensitivity with which to test treatment effect and little sensitivity to test carryover or time effect. When negative, the opposite is observed. The correlation level in a crossover comparison is a major determinant of the sensitivity of testing. Treatments from one class with one mode of action frequently have a positive correlation and should be particularly considered for crossover comparisons. With treatment comparisons of totally different classes of drugs/modes of action, the opposite is true. It is hoped that this work affects the design of future crossover trials.

Algorithms↗

PubMedDate not supplied

Chronic nitrate therapy in patients with angina with comorbidity.

In a retrospective study from the Dutch Mononitrate Quality of Life (DUMQOL) Study Group, the authors found that patients with angina with concomitant diabetes or hypercholesterolemia derived more benefit from changing over to a once-daily nitrate treatment regimen than did patients without angina. The aim of this study was to assess this issue prospectively. In an open-label study, patients with stable angina pectoris from facilities in Germany, Portugal, and me Czech Republic were treated for 3 months with multiple daily doses and subsequently for 3 more months with once-daily isosorbide mononitrate/dinitrate. After the first and second 3-month periods, they were assessed by a validated QOL battery including domains for mobility, side effects, life satisfaction, anginal pain, and psychological distress. In the 1045 patients who participated in the study, the mean summary domain scores varied from 5 to 16 points and score improvements from 1.6 to 4.3 points. In the patients without concomitant hypertension and smokers, domain scores improved less than they did in the patients without, with differences in domain score improvements up to 1.0 points (P<0.001), which is substantial considering the range of improvement was between 1.6 and 4.3 points. In the patients with diabetes mellitus or hypercholesterolemia, a reverse pattern was observed with differences in domain score improvements up to 0.4 points (P<0.05). Patients with angina with diabetes or hypercholesterolemia derived more benefit from an asymmetric regimen of isosorbide mononitrate/dinitrate than did patients without. Patients with angina with hypertension and smokers benefited less. Differences in endothelial function may be involved.

Aged↗

PubMedDate not supplied

The value of pretreatment clinical and biochemical parameters in staging and prognostic stratification of patients with newly diagnosed prostate carcinoma.

PURPOSE: To determine whether it is possible to select patients in whom and for what reason bone scintigraphy should be performed or not, a retrospective study was performed of 161 consecutive patients with newly diagnosed prostate cancer. MATERIALS AND METHODS: Follow-up varied from 1 to 88 months during which 67 patients died. Bone scans were classified from 0 (= normal) to 3 (typical pattern of metastases) and were correlated with age, alkaline phosphatase (AP), prostate specific antigen (PSA), tumor grade, TNM-stage and survival. For survival, 68 patients who were not referred for bone scintigraphy were also evaluated. RESULTS: All parameters demonstrated a correlation with the incidence of a positive bone scan, but PSA was the best overall predictor in this (p < 0.0001). None of the patients with PSA < or = 20 ng/ml (n = 64) showed metastases, whereas 8 of 9 patients with PSA > 1000 ng/ml and patients with PSA values between 20 and 1000 ng/ml in combination with AP > 90 U/L (n = 24) had bone metastases. Furthermore, a class 3 bone scan was found to be the most important parameter in assessing prognosis and survival (p < 0.0001), whereas no differences were found in patients with a class 0, 1 and 2 scintigram. CONCLUSIONS: For staging and prognostic stratification purposes, bone scintigraphy and additional roentgenograms are of value in a selected group of patients. In contrast with a typical pattern of metastases on bone scintigraphy, an abnormal scan (class 1 and 2) at the time of diagnosis is not a poor prognostic parameter of the risk of death. Bone scintigraphy can be omitted in patients with PSA values < 20 ng/ml. In patients with PSA levels > 1000 ng/ml or less increased levels combined with alkaline phosphatase levels > 90 U/L, bone scintigraphy seems to be of no value in staging disease.

Aged↗

PubMedDate not supplied

P53 and radiotherapy for oesophageal carcinoma: A comparison between 4 different antibodies.

Wild-type p53 protein plays an important role in the cellular response to ionising radiation and other DNA damaging agents and is mutated in many human tumours. Immunohistochemistry is a rapid method to detect elevated protein levels. The p53 status in a group of patients treated by radiotherapy exclusively for oesophagus carcinoma was examined and correlated with pre-treatment parameters and treatment outcome with regard to overall survival, local recurrence-free survival and distant metastases-free survival. Four different antibodies were used to evaluate their predictive power to detect p53 expression. Immunostaining for p53 protein with 4 different antibodies was performed on paraffin-embedded specimens from 69 patients with adenocarcinoma and squamous cell carcinoma of the oesophagus. All patients were treated with radiotherapy exclusively, consisting of external irradiation combined with intraluminal brachytherapy. Detection of p53 using the antibody (DO7) was significantly correlated with overall survival and distant metastases-free survival. For local recurrence-free survival no statistical significance was reached. The use of the other 3 antibodies all showed the same trend with regard to distant metastases, however statistical significance was not reached. The use of multiple antibodies did not increase the predictive value of DO7. Both for survival and metastases-free survival the use of DO7 alone was sufficient as a significant prognostic factor. We conclude that in this series, only the use of DO7 was correlated with prognosis in oesophagus carcinoma treated by radiotherapy only and that addition of 3 antibodies did not improve the predictive power.

Adenocarcinoma↗

PubMedDate not supplied

The influence of pre-operative radiotherapy on the expression of p53 and adhesion molecules: correlation with treatment results in patients with squamous cell carcinoma or adenocarcinoma.

E-cadherin and the catenins are responsible for inter-cellular adhesion in epithelial tissues. E-cadherin and/or catenin expression is often altered in malignancies, leading to increased invasiveness and metastatic activity of tumour cells. Intact adhesion molecules reduce the risk on distant metastases. This is confirmed by studies mostly performed on surgical series, correlating e-cadherin expression in tumours with prognosis and treatment outcome. It has become more apparent that anti-cancer treatment by itself can also affect the expression of adhesion molecules. We therefore suggest that the prognostic value of e-cadherin expression may depend on the treatment modality and the sequence of therapies administered for malignant tumours. We used paraffin embedded specimens from patients with rectal tumours and patients with laryngeal tumours treated by short course radiotherapy before definitive surgery. Expression of p53, e-cadherin, and beta-catenin was determined in pre-radiotherapy biopsies and in the surgical specimens. Material was available from 37 patients. We found no correlation between the expression of p53, e-cadherin or beta-catenin and pre-treatment parameters. Mutated p53 in pre-radiation biopsy correlated with increased occurrence of distant metastases and there was an unexpected trend for abnormal e-cadherin expression to correlate with reduced metastases. The prognostic value of p53 no longer existed after examination of the surgical specimens (post-radiotherapy). There was a trend for e-cadherin to reverse from abnormal to normal expression in laryngeal squamous cell carcinomas after radiotherapy, in 5/7 cases it was accompanied with p53 conversion from positive to negative expression. Based on this study it is suggested that the predictive value of the e-cadherin expression for the occurrence of distant metastases in tumours treated by radiotherapy before surgery may be different from that found in tumours treated by surgery only. This may be related to the influence of radiotherapy on e-cadherin expression, especially in squamous cell carcinomas. Alteration in p53 expression was of predictive value only in pre-treatment biopsies and the beta-catenin status did not correlate with treatment outcome in this series.

Adenocarcinoma↗

PubMedDate not supplied

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF).

The diagnostic value of immediate post-exercise left ventricular ejection fraction (LVEF) was assessed in 161 patients at rest, during maximal exercise, and immediately post-exercise by radionuclide angiography. Fifteen patients had a second examination, giving a total of 176 radionuclide examinations. Additionally, the correlation between post-exercise LVEF and physical validity was investigated. Sixty-one patients (35%) with a recent myocardial infarction (less than 4 weeks), 66 patients (37%) with an old myocardial infarction (greater than 4 weeks), and 21 patients (12%) with valvular lesions were studied. Twenty-eight patients (16%) with an abdominal aneurysm were considered as controls based on history and a normal resting and exercise electrocardiogram (ECG). LVEF and a cumulative regional wall motion (RWM) score for three regions were obtained. LVEF post-exercise was significantly increased compared to LVEF at maximal exercise in all four diagnostic groups. Absolute LVEF values were significantly dependent on the level of exercise. We conclude that immediate post-exercise LVEF should not be used for separating patients with and without coronary artery disease.

Adult↗

PubMedDate not supplied

Differential effects of unilateral magnetic cortical stimulation on reaction time.

Data from patients with brain lesions suggested that the right hemisphere is involved in the intention of simple movements, while the left is involved in more complex tasks. The contributions of each hemisphere to a reaction time (RT) task were assessed with cortical magnetic stimulation in five healthy right-handed subjects. Subjects were asked to push buttons with both hands as fast as possible after a visual start stimulus. At three different delays (25, 50 and 75 ms) after the start signal, a magnetic stimulus of 20, 40 or 60% of maximum intensity was given to either the right or the left hemisphere. Delay, intensity and side of stimulation varied in random order. Repeated measures analysis of variance showed two main effects: firstly, RT was longer on the body side innervated by the stimulated than by the non-stimulated hemisphere. Thus, cortical stimulation delayed the execution of a motor task, as shown previously. Secondly, there was an interaction between side of stimulation and delay of the cortical stimulus. At a delay of 25 ms, right-sided stimulation resulted in longer RTs than left-sided stimulation. At delays of 50 and 75 ms, the reverse proved true. In both cases the effect held for both hands. According to these results, the right hemisphere is predominantly involved in the early phases of an RT task, while the left hemisphere is more involved in later phases of processing. The results show that cortical magnetic stimulation can be used to investigate differential contributions of the hemispheres to motor tasks in vivo.

Adult↗

PubMedDate not supplied

The diagnostic value of pretreatment serum LDH in patients with limited disease small-cell lung carcinoma.

BACKGROUND: In patients with limited disease SCLC, the overall survival is still poor. Therefore, a retrospective study was performed involving 48 patients with limited disease SCLC to select a parameter which can identify prognostic subgroups at the time of diagnosis. MATERIALS AND METHODS: Follow-up ranged from 3 to 96 months, during which period 38 patients died. Based on clinical outcome, patients were classified into 3 groups: complete remission (CR) (n = 16), local recurrence (LOC) (n = 7) and distant recurrence (DIS) (n = 25). Age, gender and pretreatment biochemical parameters were correlated with clinical outcome and survival. For survival 70 patients staged as having extensive disease (ED) served as a control group. RESULTS: No differences in survival were found in patients with LOC (14% 2 year survival) and DIS (16% 2-year survival) (p = 0.67). Patients achieving a complete remission had a significantly better survival (75% two-year survival). LDH was found to be the only significant correlate of both tumor progression and survival. All patients with pretreatment LDH levels < 240 U/L (n = 13) had tumor recurrence. The survival rate of patients with LDH levels, 240 U/L (41% 2-year survival) was much better than that of patients with LDH levels > 240 U/L 8% 2-year survival) (p = 0.0001). No significant difference in survival (p = 0.33) was found between patients with LD and LDH > 240 U/L and patients with ED and LDH < 400 U/L. Patients with ED and LDH values > 400 U/L showed the poorest outcome. CONCLUSION: LDH may be used for the identification of prognostic subgroups in SCLC. Patients showing pretreatment LDH levels > 240 U/L have an extremely high risk of tumor recurrence, while their survival is poor and comparable to that of patients staged as having extensive disease and LDH values < 400 U/L.

Adult↗